In addition, PDE4 inhibitors can also directly enhance network plasticity and attenuate degenerative processes and cognitive dysfunction by increasing activity of the canonical cAMP/phosphokinase-A/cAMP Responsive Element Binding protein (cAMP/PKA/CREB) plasticity pathway.
A more thorough understanding of systemic dysregulation of CREB in AD will facilitate the search for a biomarker of cognitive function in AD, and also aid in the understanding of the mechanisms underlying cognitive decline in AD.
The key findings of the present study demonstrated that CREB1 gene silencing results in aggravated VD that occurs as a result of inhibiting the PKA-CREB signaling pathway, thus exasperating cognitive dysfunction.
Importantly, hippocampal cyclic adenosine monophosphate (cAMP), p-PKA, p-CREB and BDNF levels were significantly increased in the APP/PS1 mice after RJ treatment, indicating that the cAMP/PKA/CREB/BDNF pathway might be related to the ameliorative effect of RJ on cognitive decline.
Administration of rolipram improved the memory deficits with concomitant recovery of cAMP and phosphorylated CREB levels, suggesting that reduced cAMP/CREB signaling in the DG leads to cognitive impairment in MPTP-treated mice.
Taken together, our data demonstrated that the reversal effect of FFPM on cognitive deficits in APP/PS1 transgenic mice might be related to stimulation of the cAMP/PKA/CREB/BDNF pathway and anti-inflammatory effects.
Extremely low frequency electromagnetic field exposure causes cognitive impairment associated with alteration of the glutamate level, MAPK pathway activation and decreased CREB phosphorylation in mice hippocampus: reversal by procyanidins extracted from the lotus seedpod.
We also discuss the development of novel therapeutic strategies based on CREB targeting to ameliorate cognitive decline in aging and cognitive disorders.
Finally, we will discuss novel therapeutic approaches targeted to CBP/CREB function for treating the cognitive dysfunction of RTS and other neurological disorders.